Luminal breast cancer metastasis is dependent on estrogen signaling.

Luminal breast cancer is the most frequently encountered type of human breast cancer and accounts for half of all breast cancer deaths due to metastatic disease. We have developed new in vivo models of disseminated human luminal breast cancer that closely mimic the human disease. From initial lesions in the tibia, locoregional metastases develop predictably along the iliac and retroperitoneal lymph node chains.

Transforming growth factor-beta signaling: emerging stem cell target in metastatic breast cancer?

In most human breast cancers, lowering of TGFbeta receptor- or Smad gene expression combined with increased levels of TGFbetas in the tumor microenvironment is sufficient to abrogate TGFbetas tumor suppressive effects and to induce a mesenchymal, motile and invasive phenotype. In genetic mouse models, TGFbeta signaling suppresses de novo mammary cancer formation but promotes metastasis of tumors that have broken through TGFbeta tumor suppression. In mouse models of "triple-negative" or basal-like breast cancer, treatment with TGFbeta neutralizing antibodies or receptor kinase inhibitors strongly inhibits development of lung- and bone metastases.

Canonical Wnt signaling: an unexpected new player.

Canonical Wnt signaling, below the Fz/LRP receptor complex, induces the stabilization of beta-catenin via an unresolved mechanism. A recent study in Genes & Development introduces a new player and deepens our understanding of this signaling relay that plays pivotal roles during embryogenesis and tumorigenesis.

Concurrent chemo-radiation in the conservative management of breast cancer.

Purpose: Sequencing of chemotherapy (CTX) with radiation (RT) in the conservative management of breast cancer (CS+RT) remains controversial. We report here the results of a retrospective analysis of all patients treated with CTX and RT, with specific focus on outcome as a function of sequencing of CTX with RT.

Methods And Materials: A total of 535 patients treated with CS+RT received CTX as a component of therapy.

Selective inhibitors of type I receptor kinase block cellular transforming growth factor-beta signaling.

Transforming growth factor (TGFbeta) is a 25-kDa dimeric polypeptide that plays a key role in a variety of physiological processes and disease states. Blocking TGFbeta signaling represents a potentially powerful and conceptually novel approach to the treatment of disorders in which the signaling pathway is constitutively activated, such as cancer, chronic inflammation with fibrosis and select immune disorders. In this paper, we describe the biological properties of a novel series of quinazoline-derived inhibitors of the type I transforming growth factor receptor kinase (TbetaKIs) that bind to the ATP-binding site and keep the kinase in its inactive conformation.